PROM2

Summary

PROM2 (prominin 2, HGNC:20685) is a protein-coding gene on chromosome 2q11.1, encoding Prominin-2 (Q8N271).

This gene encodes a member of the prominin family of pentaspan membrane glycoproteins. The encoded protein localizes to basal epithelial cells and may be involved in the organization of plasma membrane microdomains. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 150696 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 186 total
• MANE Select transcript: NM_001165978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20685
Approved symbol	PROM2
Name	prominin 2
Location	2q11.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000155066
Ensembl biotype	protein_coding
OMIM	617160
Entrez	150696

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000317620, ENST00000317668, ENST00000403131, ENST00000431567, ENST00000462029, ENST00000463580, ENST00000477767, ENST00000478295, ENST00000487138, ENST00000495540, ENST00000497110, ENST00000873399, ENST00000873400, ENST00000873401, ENST00000873402, ENST00000873403

RefSeq mRNA: 4 — MANE Select: NM_001165978 NM_001165977, NM_001165978, NM_001321070, NM_144707

CCDS: CCDS2012

Canonical transcript exons

ENST00000317620 — 24 exons

Exon	Start	End
ENSE00001209540	95289224	95291302
ENSE00003469985	95288933	95289006
ENSE00003506280	95284969	95285115
ENSE00003506393	95286804	95286857
ENSE00003513626	95275930	95276132
ENSE00003517943	95278721	95278784
ENSE00003524473	95282142	95282226
ENSE00003545788	95277930	95278004
ENSE00003546149	95276972	95277061
ENSE00003566633	95279845	95279997
ENSE00003578454	95286479	95286571
ENSE00003587659	95276227	95276347
ENSE00003601191	95288483	95288589
ENSE00003605587	95276594	95276657
ENSE00003620206	95278985	95279144
ENSE00003624900	95281242	95281365
ENSE00003651144	95288211	95288300
ENSE00003656556	95281925	95282016
ENSE00003661836	95275461	95275510
ENSE00003667078	95285639	95285710
ENSE00003684195	95287396	95287464
ENSE00003689768	95287133	95287213
ENSE00003843074	95274449	95274829
ENSE00003890373	95277364	95277566

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 99.06.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8199 / max 111.5559, expressed in 316 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21423	2.2047	305
21422	0.5638	211
202301	0.0514	26

Top tissues by expression

242 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	99.06	gold quality
gingival epithelium	UBERON:0001949	98.88	gold quality
gingiva	UBERON:0001828	98.54	gold quality
palpebral conjunctiva	UBERON:0001812	98.32	gold quality
corpus epididymis	UBERON:0004359	98.16	gold quality
oviduct epithelium	UBERON:0004804	97.69	gold quality
lower esophagus mucosa	UBERON:0035834	97.68	gold quality
buccal mucosa cell	CL:0002336	97.35	gold quality
esophagus mucosa	UBERON:0002469	97.23	gold quality
oral cavity	UBERON:0000167	96.32	gold quality
renal medulla	UBERON:0000362	95.78	gold quality
upper leg skin	UBERON:0004262	94.81	gold quality
skin of hip	UBERON:0001554	94.72	gold quality
seminal vesicle	UBERON:0000998	94.67	gold quality
zone of skin	UBERON:0000014	94.53	gold quality
skin of abdomen	UBERON:0001416	94.47	gold quality
skin of leg	UBERON:0001511	94.46	gold quality
mammalian vulva	UBERON:0000997	94.12	gold quality
mouth mucosa	UBERON:0003729	93.77	gold quality
gall bladder	UBERON:0002110	93.34	gold quality
minor salivary gland	UBERON:0001830	93.28	gold quality
pharyngeal mucosa	UBERON:0000355	93.26	gold quality
saliva-secreting gland	UBERON:0001044	92.94	gold quality
nasal cavity epithelium	UBERON:0005384	92.84	gold quality
mammary duct	UBERON:0001765	92.78	gold quality
epithelium of mammary gland	UBERON:0003244	92.71	gold quality
cauda epididymis	UBERON:0004360	92.24	gold quality
vagina	UBERON:0000996	91.68	gold quality
parotid gland	UBERON:0001831	91.54	gold quality
metanephros cortex	UBERON:0010533	90.91	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting PROM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-5683	99.36	68.59	2083

Literature-anchored findings (GeneRIF, showing 12)

• identification as well as molecular and cell biological characterization (PMID:12514187)
• The PROM2 gene was shown to effectively separate these two tumor(chromophobe renal cell carcinoma (RCC) and benign oncocytoma) groups by quantitative reverse transcription-PCR using fresh tissue samples, with similar trends seen on formalin-fixed tissues. (PMID:17145811)
• Prominin-2 is widely and abundantly expressed along the epithelia of various segments of the adult male genitourinary tract. (PMID:18536929)
• prominin-2, another protein in the same family as CD133/prominin-1, may not play an important functional role in the growth of human glioma and hepatocellular carcinoma cells (PMID:19724856)
• Data show the distribution and subcellular localization of prominin-2 within the kidney in situ and its release into the urine. (PMID:20333396)
• Prom2 protrusions primarily localize to lipid rafts and recruit cholesterol into protrusions and away from caveolae, leading to increased phosphorylation of caveolin-1, which inhibits Cdc42-dependent endocytosis (PMID:23583380)
• PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis. (PMID:31164716)
• Prominin2 facilitates ferroptosis resistance in epithelial and carcinoma cells. Prominin2 promotes formation of ferritin-containing multivesicular bodies and exosomes. (PMID:31735663)
• PROM2 promotes gemcitabine chemoresistance via activating the Akt signaling pathway in pancreatic cancer. (PMID:32123287)
• LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer. (PMID:34728613)
• Prominin 2 decreases cisplatin sensitivity in non-small cell lung cancer and is modulated by CTCC binding factor. (PMID:37665741)
• PROM2 overexpression induces metastatic potential through epithelial-to-mesenchymal transition and ferroptosis resistance in human cancers. (PMID:38515278)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	prom2	ENSDARG00000039406
mus_musculus	Prom2	ENSMUSG00000027376
rattus_norvegicus	Prom2	ENSRNOG00000014710
drosophila_melanogaster	promL	FBGN0026189
drosophila_melanogaster	CG45067	FBGN0266437
caenorhabditis_elegans		WBGENE00008571

Paralogs (1): PROM1 (ENSG00000007062)

Protein

Protein identifiers

Prominin-2 — Q8N271 (reviewed: Q8N271)

Alternative names: Prominin-like protein 2

All UniProt accessions (2): Q8N271, F8WDW5

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Binds cholesterol.

Subcellular location. Apical cell membrane. Basolateral cell membrane. Cell projection. Microvillus membrane. Cilium membrane.

Tissue specificity. Present in saliva within small membrane particles (at protein level). Expressed in kidney, prostate, trachea, esophagus, salivary gland, thyroid gland, mammary gland adrenal gland, placenta, stomach, spinal cord and liver. In submucosal tumor, expressed in spindle-shaped or stellate stromal cells. Expressed in prostate cancer cell lines.

Post-translational modifications. Glycosylated.

Similarity. Belongs to the prominin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N271-1	1	yes
Q8N271-2	2
Q8N271-3	3

RefSeq proteins (4): NP_001159449, NP_001159450, NP_001307999, NP_653308 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008795	Prominin	Family

Pfam: PF05478

UniProt features (23 total): topological domain 6, transmembrane region 5, sequence conflict 4, modified residue 2, splice variant 2, signal peptide 1, chain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N271-F1	86.00	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 727, 818

Glycosylation sites (1): 270

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): RNGTGGGC_UNKNOWN, GOBP_PINOCYTOSIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, BILD_SRC_ONCOGENIC_SIGNATURE, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, RICKMAN_METASTASIS_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3

GO Biological Process (5): positive regulation of protein phosphorylation (GO:0001934), positive regulation of cell projection organization (GO:0031346), regulation of GTPase activity (GO:0043087), negative regulation of pinocytosis (GO:0048550), negative regulation of caveolin-mediated endocytosis (GO:2001287)

GO Molecular Function (2): cholesterol binding (GO:0015485), protein binding (GO:0005515)

GO Cellular Component (15): plasma membrane (GO:0005886), microvillus (GO:0005902), cilium (GO:0005929), cell surface (GO:0009986), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), cytoplasmic vesicle (GO:0031410), microvillus membrane (GO:0031528), cell projection (GO:0042995), microspike (GO:0044393), ciliary membrane (GO:0060170), extracellular exosome (GO:0070062), prominosome (GO:0071914), membrane (GO:0016020), membrane raft (GO:0045121)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of endocytosis	2
plasma membrane bounded cell projection	2
plasma membrane region	2
cell projection membrane	2
extracellular vesicle	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
cell projection organization	1
regulation of cell projection organization	1
positive regulation of cellular component organization	1
GTPase activity	1
regulation of hydrolase activity	1
pinocytosis	1
regulation of pinocytosis	1
caveolin-mediated endocytosis	1
regulation of caveolin-mediated endocytosis	1
sterol binding	1
alcohol binding	1
binding	1
membrane	1
cell periphery	1
actin filament bundle	1
actin-based cell projection	1
intraciliary transport particle	1
membrane-bounded organelle	1
basal plasma membrane	1
apical part of cell	1
cytoplasm	1
intracellular vesicle	1
microvillus	1
cilium	1
bounding membrane of organelle	1
membrane microdomain	1

Protein interactions and networks

STRING

772 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PROM2	NCOA4	Q13772	464
PROM2	C1orf159	Q96HA4	459
PROM2	DNHD1	Q96M86	433
PROM2	MTF1	Q14872	432
PROM2	SLC40A1	Q9NP59	427
PROM2	PTCD2	Q8WV60	422
PROM2	ZNHIT2	Q9UHR6	418
PROM2	CISD1	Q9NZ45	418
PROM2	AIFM2	Q9BRQ8	412
PROM2	ZNF106	Q9H2Y7	410
PROM2	FRMD8	Q9BZ67	410
PROM2	BOD1L1	Q8NFC6	406
PROM2	FRRS1L	Q9P0K9	404
PROM2	GPX4	P36969	400
PROM2	ACSL4	O60488	393

IntAct

8 interactions, top by confidence:

A	B	Type	Score
PROM2	GPR152	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	PROM2	psi-mi:“MI:0915”(physical association)	0.560
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
PROM2	GPR152	psi-mi:“MI:0915”(physical association)	0.000
PROM2	AMIGO1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): PROM2 (Proximity Label-MS), PROM2 (Affinity Capture-RNA), PROM2 (Proximity Label-MS), PROM2 (Affinity Capture-RNA), GPR152 (Two-hybrid), AMIGO1 (Two-hybrid), PROM2 (Negative Genetic), PROM2 (Affinity Capture-MS), PROM2 (Affinity Capture-RNA), PROM2 (Affinity Capture-MS)

ESM2 similar proteins: A7MBM2, E9PY61, O00391, O08542, O60894, O60895, O76095, O77049, O88824, P52798, Q15904, Q16586, Q5Q0T9, Q5RJL6, Q641Q3, Q6IUU3, Q6P5F7, Q6PRD1, Q6UWJ8, Q6ZVN8, Q6ZVW7, Q7TQ32, Q80YF6, Q864V4, Q867C0, Q86WC4, Q8BGT0, Q8BH06, Q8BND5, Q8C1Q4, Q8K4C2, Q8N271, Q8N7M5, Q8NAC3, Q8R4C4, Q8R4C5, Q8R4C6, Q8VE43, Q91ZV8, Q96F46

Diamond homologs: Q3UUY6, Q8CJ52, Q8N271

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

186 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	144
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4331 predictions. Top by Δscore:

Variant	Effect	Δscore
2:95274826:TCAGG:T	donor_loss	1.0000
2:95274828:AGGT:A	donor_loss	1.0000
2:95274829:GGTG:G	donor_loss	1.0000
2:95274830:G:GA	donor_loss	1.0000
2:95275460:GA:G	acceptor_gain	1.0000
2:95276130:GCT:G	donor_gain	1.0000
2:95276133:G:GG	donor_gain	1.0000
2:95276348:G:GG	donor_gain	1.0000
2:95277489:G:GT	donor_gain	1.0000
2:95277504:G:GT	donor_gain	1.0000
2:95277923:A:AG	acceptor_gain	1.0000
2:95277925:TTCA:T	acceptor_loss	1.0000
2:95277926:TCA:T	acceptor_loss	1.0000
2:95277928:A:AG	acceptor_gain	1.0000
2:95277928:AG:A	acceptor_gain	1.0000
2:95277928:AGGT:A	acceptor_gain	1.0000
2:95277929:G:A	acceptor_loss	1.0000
2:95277929:G:GA	acceptor_gain	1.0000
2:95277929:GG:G	acceptor_gain	1.0000
2:95277929:GGT:G	acceptor_gain	1.0000
2:95277929:GGTG:G	acceptor_gain	1.0000
2:95278001:GGAG:G	donor_gain	1.0000
2:95278002:GAGG:G	donor_gain	1.0000
2:95278003:AG:A	donor_loss	1.0000
2:95278004:GGTGA:G	donor_loss	1.0000
2:95278006:T:G	donor_loss	1.0000
2:95278984:GA:G	acceptor_gain	1.0000
2:95279119:G:GT	donor_gain	1.0000
2:95279839:TGGCA:T	acceptor_loss	1.0000
2:95279840:GGCAG:G	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000495096 (2:95286327 A>G), RS1000757296 (2:95273793 G>A), RS1001013733 (2:95286701 C>G,T), RS1001245931 (2:95289082 G>A,T), RS1001488315 (2:95276841 C>A,T), RS1001916471 (2:95277043 G>A,T), RS1002454867 (2:95281704 C>T), RS1002655737 (2:95287887 ATG>A,ATGTG), RS1002839263 (2:95275613 C>G), RS1002948030 (2:95291008 T>C), RS1003006676 (2:95284318 G>C), RS1003123031 (2:95284596 C>T), RS1003562939 (2:95277794 G>A), RS1003853525 (2:95280888 C>T), RS1003884903 (2:95275242 G>A)

Disease associations

OMIM: gene MIM:617160 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases methylation, affects cotreatment, decreases expression	4
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance, increases expression	2
Mustard Gas	increases expression, increases phosphorylation	2
Tobacco Smoke Pollution	affects expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bufotalin	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sulforaphane	decreases expression	1
ferrous chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Calcitriol	increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Endosulfan	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Nicotine	increases expression	1
Sodium Chloride	affects localization, decreases expression, increases expression, affects cotreatment	1
Testosterone	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	decreases methylation	1
Gold Compounds	increases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.